Details of the Drug Combination

General Information of Drug Combination (ID: DC5B21I)

• Drug Combination Name: Betamethasone Valerate + Ruxolitinib
• Indication: Hodgkin lymphoma; Status: Investigative [1]
• Component Drugs:
  Betamethasone Valerate (DMMIAXO): Small molecular drug
  Ruxolitinib (DM7Q98D): Small molecular drug
• High-throughput Screening Result:
  Testing Cell Line: L-1236
  Zero Interaction Potency (ZIP) Score: 16.16
  Bliss Independence Score: 15.76
  Loewe Additivity Score: 6.1
  LHighest Single Agent (HSA) Score: 20.83

Molecular Interaction Atlas of This Drug Combination

Indication(s) of Betamethasone Valerate

Disease Entry	ICD 11	Status	REF
Dermatological disease	DA24.Y	Approved	[2]

Betamethasone Valerate Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Glucocorticoid receptor (NR3C1)	TTYRL6O	GCR_HUMAN	Modulator	[8]

Betamethasone Valerate Interacts with 2 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
Cytochrome P450 3A4 (CYP3A4)	DE4LYSA	CP3A4_HUMAN	Metabolism	[9]
Corticosteroid 11-beta-dehydrogenase 2 (HSD11B2)	DEDH7FP	DHI2_HUMAN	Metabolism	[10]

Betamethasone Valerate Interacts with 9 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Interferon gamma (IFNG)	OTXG9JM7	IFNG_HUMAN	Decreases Expression	[11]
Granulocyte-macrophage colony-stimulating factor (CSF2)	OT1M7D28	CSF2_HUMAN	Decreases Expression	[11]
Interleukin-4 (IL4)	OTOXBWAU	IL4_HUMAN	Decreases Expression	[11]
Interleukin-5 (IL5)	OTAFPSCO	IL5_HUMAN	Decreases Expression	[11]
Interleukin-3 (IL3)	OT0CQ35N	IL3_HUMAN	Decreases Expression	[11]
Tumor necrosis factor receptor superfamily member 5 (CD40)	OT5YU2XB	TNR5_HUMAN	Decreases Expression	[12]
T-lymphocyte activation antigen CD86 (CD86)	OTJCSBPC	CD86_HUMAN	Decreases Expression	[12]
Interleukin-2 (IL2)	OTGI4NSA	IL2_HUMAN	Decreases Expression	[11]
CD83 antigen (CD83)	OT1V4WQF	CD83_HUMAN	Decreases Expression	[12]

Indication(s) of Ruxolitinib

Disease Entry	ICD 11	Status	REF
Essential thrombocythemia	3B63.1Z	Approved	[3]
High-risk myelofibrosis	2A20.2	Approved	[4]
Myelofibrosis	2A22	Approved	[2]
Myeloproliferative neoplasm	2A20	Approved	[5]
Coronavirus Disease 2019 (COVID-19)	1D6Y	Phase 3	[6]
Pancreatic cancer	2C10	Phase 3	[4]
Atopic dermatitis	EA80	Phase 1/2	[7]
Vitiligo	ED63.0	Phase 1/2	[7]

Ruxolitinib Interacts with 5 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Janus kinase 2 (JAK-2)	TTRMX3V	JAK2_HUMAN	Modulator	[13]
Janus kinase 1 (JAK-1)	TT6DM01	JAK1_HUMAN	Modulator	[13]
Urokinase plasminogen activator surface receptor (PLAUR)	TTPRL03	UPAR_HUMAN	Inhibitor	[14]
HUMAN janus kinase 1 (JAK-1)	TTWKB01	JAK1_HUMAN	Inhibitor	[15]
HUMAN janus kinase 2 (JAK-2)	TT0F5HE	JAK2_HUMAN	Inhibitor	[15]

Ruxolitinib Interacts with 1 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Mitogen-activated protein kinase 14 (MAPK14)	OT5TCO3O	MK14_HUMAN	Increases ADR	[16]

References

• [1] Loss of function mutations in VARS encoding cytoplasmic valyl-tRNA synthetase cause microcephaly, seizures, and progressive cerebral atrophy.Hum Genet. 2018 Apr;137(4):293-303. doi: 10.1007/s00439-018-1882-3. Epub 2018 Apr 24.
• [2] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
• [3] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [4] URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 5688).
• [5] Ruxolitinib FDA Label
• [6] Incyte begins Phase III trial of ruxolitinib to treat Covid-19. 20.April.2020.
• [7] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [8] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
• [9] Studies on Drug Interactions between CYP3A4 Inhibitors and Glucocorticoids.
• [10] Metabolism of synthetic steroids by the human placenta. Placenta. 2007 Jan;28(1):39-46.
• [11] Tacrolimus suppressed the production of cytokines involved in atopic dermatitis by direct stimulation of human PBMC system. (Comparison with steroids). Int Immunopharmacol. 2001 Jun;1(6):1219-26. doi: 10.1016/s1567-5769(01)00059-5.
• [12] Pimecrolimus leads to an apoptosis-induced depletion of T cells but not Langerhans cells in patients with atopic dermatitis. J Allergy Clin Immunol. 2005 Jun;115(6):1276-83. doi: 10.1016/j.jaci.2005.02.011.
• [13] 2011 FDA drug approvals. Nat Rev Drug Discov. 2012 Feb 1;11(2):91-4.
• [14] Urokinase-type plasminogen activator receptor signaling is critical in nasopharyngeal carcinoma cell growth and metastasis.Cell Cycle. 2014;13(12):1958-69.
• [15] The Use of Anti-Inflammatory Drugs in the Treatment of People With Severe Coronavirus Disease 2019 (COVID-19): The Perspectives of Clinical Immunologists From China. Clin Immunol. 2020 May;214:108393.
• [16] ADReCS-Target: target profiles for aiding drug safety research and application. Nucleic Acids Res. 2018 Jan 4;46(D1):D911-D917. doi: 10.1093/nar/gkx899.